Biological mediators isolated from tumor tissue and possibly associated with tumor development, blood flow, and growth and under study. Particular attention is directed toward an acid protease system which directly, or indirectly through formation of vasoactive polypeptide (kinin) mediators may influence cellular control mechanisms within the tumor tissue. An acid protease, isolated from the transplanted rodent Mruphy-Sturm lymphosarcoma tumor, will continue to be purified further to allow for its full biochemical characterization relative to enzyme kinetics, active sites, vasopeptides formed, and effect of protease inhibitors. The kininogen substrate also will be purified further to permit its characterization, including the molecular weight determination of both substrate and enzymes. Purification of the kinins also will be carried out, their chemical nature studied, and their effects on the vascular system, membrane permeability, vasculogenesis, and chemotaxis studied by in vivo and in situ techniques. The cellular sites of localization of the key components of the protease system will be investigated. The relationship of the tumor acid protease to those acid proteases found in normal rodent tissue (liver, spleen, lung) will be studied as will the effect of body and tissue development and select inhibitors on the levels of key components of the system in tumor-bearing and normal animals. It is hoped that these studies will provide some understanding of the possible role of proteases within tumor tissue and that the inhibitor studies will suggest a new chemotherapeutic approach.